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    Summary
    EudraCT Number:2014-003625-17
    Sponsor's Protocol Code Number:CA205-275
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-03-07
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2014-003625-17
    A.3Full title of the trial
    A phase II single arm clinical trial of nivolumab (BMS-936558) in subjects with metastatic or unresectable urothelial cancer who have progressed or recurred following treatment with a platinum agent
    Studio clinico di fase II, a braccio singolo, di nivolumab (BMS-936558) in soggetti affetti da carcinoma uroteliale metastatico o non resecabile con progressione o recidiva di malattia dopo trattamento con un agente a base di platino.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of nivolumab in participants with metastatic or unresectable bladder cancer
    Studio di Nivolumab in soggetti affetti da tumore della vescica metastatico o non resecabile
    A.4.1Sponsor's protocol code numberCA205-275
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
    B.1.3.4CountryBelgium
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBristol-Myers Squibb International Corporation - Belgio
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBristol-Myers Squibb International Corporation
    B.5.2Functional name of contact pointGCT-SU
    B.5.3 Address:
    B.5.3.1Street AddressParc de l'Alliance - Avenue de Finlande, 4
    B.5.3.2Town/ cityBraine-l'Alleud
    B.5.3.3Post code1420
    B.5.3.4CountryBelgium
    B.5.4Telephone number32 2 352 7416
    B.5.5Fax number32 2 352 7164
    B.5.6E-mailclinical.trials@bms.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameNivolumab
    D.3.2Product code BMS-936558
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNivolumab
    D.3.9.1CAS number 946414-94-4
    D.3.9.2Current sponsor codeBMS-936558-01
    D.3.9.3Other descriptive nameNIVOLUMAB
    D.3.9.4EV Substance CodeSUB122750
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    metastatic or unresectable urothelial cancer
    carcinoma uroteliale metastatico o non resecabile
    E.1.1.1Medical condition in easily understood language
    metastatic or unresectable urothelial cancer
    carcinoma uroteliale metastatico o non resecabile
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10046723
    E.1.2Term Urothelial carcinoma ureter
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10046714
    E.1.2Term Urothelial carcinoma bladder
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10064467
    E.1.2Term Urothelial carcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level PT
    E.1.2Classification code 10005003
    E.1.2Term Bladder cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10046728
    E.1.2Term Urothelial carcinoma urethra
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To measure the effect of nivolumab (BMS-
    936558) in reducing tumor size in subjects with metastatic or
    unresectable bladder cancer.
    Misurare l’effetto di nivolumab (BMS-936558) nel ridurre le dimensioni del tumore in soggetti affetti da carcinoma della vescica metastatico o non resecabile.
    E.2.2Secondary objectives of the trial
    To measure the effect of nivolumab (BMS-936558) in reducing tumor size in subjects with metastatic or unresectable bladder cancer.
    Misurare l’effetto di nivolumab (BMS-936558) nel ridurre le dimensioni del tumore in soggetti affetti da carcinoma della vescica metastatico o non resecabile.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    a. Evidence of metastatic or surgically unresectable transitional cell carcinoma of the urothelium involving the bladder, urethra, ureter, or
    renal pelvis.
    b. Measurable disease by CT or MRI
    c. Progression or recurrence after treatment
    i) with at least 1 platinum-containing chemotherapy regimen for metastatic or surgically-unresectable locally advanced urothelial cancer, or
    ii) within 12 months of peri-operative (neo-adjuvant or adjuvant) treatment with platinum agent in the setting of cystectomy for localized muscle-invasive urothelial cancer.
    d)Subjects that have received more than 2 prior lines of chemotherapy
    must not have liver metastases.
    e) tumor tissue (archived or new biopsy) must be provided for biomarker analysis
    f) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
    a. Evidenza istologica o citologica di carcinoma uroteliale a cellule transizionali della vescica, dell’uretra, dell’uretere o della pelvi renale, metastatico o chirurgicamente non resecabile.
    b. malattia misurabile mediante TC o RM
    c. progressione o recidiva dopo il trattamento
    i) con almeno 1 regime chemioterapico contenente platino per carcinoma uroteliale metastatico o localmente avanzato, chirurgicamente non resecabile, oppure
    ii) entro 12 mesi da un trattamento peri-operatorio (neoadiuvante o adiuvante) con un agente a base di platino nel contesto di una cistectomia per carcinoma uroteliale muscolo-invasivo localizzato.
    d. I soggetti che abbiano ricevuto più di 2 linee precedenti di chemioterapia non dovranno presentare metastasi epatiche.
    e. si dovrà fornire tessuto tumorale (da biopsia archiviata o di nuova acquisizione) per l’analisi dei biomarcatori
    f. Performance status (PS) secondo l’Eastern Cooperative Oncology Group (ECOG) 0 o 1.
    E.4Principal exclusion criteria
    a) Subjects with active cancer that has spread to the central nervous system
    b)Any serious or uncontrolled medical disorder, that in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
    c. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
    d. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism,
    due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to
    recur in the absence of an external trigger are permitted to enroll.
    e. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement
    doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
    f. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
    g.Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration
    of study treatment.

    Exclusion laboratory criteria:
    -Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody (HCV antibody) indicating acute or chronic infection.
    - Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
    a) Metastasi attive del sistema nervoso centrale (SNC)
    b) Qualsiasi patologia medica seria o non controllata che possa, a giudizio dello sperimentatore, aumentare il rischio associato alla partecipazione allo studio o alla somministrazione del farmaco in studio, compromettere la capacità del soggetto di ricevere la terapia secondo protocollo, oppure interferire con l’interpretazione dei risultati dello studio.
    c) Pregressa patologia tumorale maligna attiva nei 3 anni precedenti, ad eccezione di tumori trattabili localmente che siano stati apparentemente curati
    d) Soggetti con malattia autoimmune in fase attiva, nota o sospetta. Potranno essere arruolati i soggetti con vitiligine, diabete mellito di tipo I, ipotiroidismo residuo dovuto a malattia autoimmune che richieda solo una terapia ormonale sostitutiva, psoriasi che non richieda un trattamento sistemico o con patologie che non si prevede possano recidivare in assenza di un fattore esterno scatenante.
    e) Soggetti con condizioni che richiedano un trattamento sistemico con corticosteroidi (> 10 mg/die di equivalenti del prednisone) o altri farmaci immunosoppressori nei 14 giorni precedenti la somministrazione del farmaco in studio. Gli steroidi per via inalatoria o topica e dosi > 10 mg/die di equivalenti del prednisone per la terapia sostitutiva dell’insufficienza surrenalica, sono consentiti in assenza di malattia autoimmune in fase attiva.
    f) Precedente trattamento con un anticorpo anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 o con qualsiasi altro anticorpo o farmaco specificamente mirato alla co-stimolazione delle cellule T o a vie di checkpoint immunitario.
    g) Trattamento con qualsiasi chemioterapia, radioterapia, agente biologico antitumorale o terapia sperimentale nei 28 giorni precedenti la prima somministrazione del trattamento in studio.
    Criteri di esclusione relativi alle analisi di laboratorio:
    - Positività al test per l’antigene di superficie del virus dell’epatite B (HBV sAg) o all’acido ribonucleico (RNA) del virus dell’epatite C o agli anticorpi anti-epatite C (anticorpi HCV), indicante un’infezione acuta o cronica.
    - Anamnesi nota di positività del test per il virus dell’immunodeficienza umana (HIV) o sindrome da immunodeficienza acquisita (AIDS) nota.
    E.5 End points
    E.5.1Primary end point(s)
    The overall response rate (using RECIST 1.1) to nivolumab (BMS-936558) based on a independent review committee in subjects with metastatic or unresectable bladder cancer
    Il tasso di risposta complessiva (utilizzando i RECIST 1.1) di Nivolumab (BMS-936558) basato sulle valutazioni di un Comitato di revisione indipendente in soggetti affetti da tumore della vescica metastatico o non resecabile
    E.5.1.1Timepoint(s) of evaluation of this end point
    Eight weeks after the subject's first dose and then every 8 weeks after up to 48 weeks, then every 12 weeks until disease progression or study drug is discontinued
    Otto settimane dopo la prima dose del soggetto e successivamente ogni 8 settimane fino alla settimana 48, poi ogni 12 settimane fino a progressione della malattia o alla discontinuazione del trattamento in studio
    E.5.2Secondary end point(s)
    To evaluate progression free survival (using RECIST 1.1) in subjects based on assessments by an independent review committee
    To evaluate overall survival in subjects as assessed by the investigator
    To estimate overall response rate (using RECIST 1.1) in subjects as assessed by the investigator
    Valutare la progressione libera da malattia (utilizzando i RECIST 1.1) in soggetti in base alla valutazione di un Comitato di revisione indipendente
    Stimare la sopravvivenza complessiva nei soggetti in base alla valutazione dello sperimentatore
    Stimare il tasso di risposta complessiva (utilizzando i RECIST 1.1) nei soggetti in base alla valutazione dello sperimentatore
    E.5.2.1Timepoint(s) of evaluation of this end point
    Eight weeks after the subject's first dose and then every 8 weeks after up to 48 weeks, then every 12 weeks until disease progression or study drug discontinued.
    Every 3 months during the survival follow-up phase up to a maximum of 5 years
    Eight weeks after the subject's first dose and then every 8 weeks after up to 48 weeks, then every 12 weeks until disease progression or study drug discontinued
    Otto settimane dopo la prima dose del soggetto e successivamente ogni 8 settimane fino alla settimana 48, poi ogni 12 settimane fino a progressione della malattia o alla discontinuazione del trattamento in studio
    ogni 3 mesi durante la fase di follow-up di sopravvivenza fino ad un massimo di 5 anni.
    Otto settimane dopo la prima dose del soggetto e successivamente ogni 8 settimane fino alla settimana 48, poi ogni 12 settimane fino a progressione della malattia o alla discontinuazione del trattamento in studio
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biomarker Assessments, Outcomes Research Assessments, Immunogenicity Assessments
    Valutazione dei biomarcatori,valutazione di outcome research e valutazione di immunogenicità
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Aperto
    Open
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Belgium
    Czech Republic
    Finland
    Germany
    Italy
    Japan
    Poland
    Spain
    Sweden
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The study will end when survival follow-up has concluded
    Lo studio terminerà quando il follow-up di sopravvivenza sarà concluso.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months11
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 153
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 153
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state16
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 306
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    At study end subjects who continue to demonstrate clinical benefit and tolerating study drug will be eligible to receive it. Study drug will be provided via study extension, rollover study or another mechanism.BMS can terminate access to study drug if:a) marketing application rejected by responsible HA;b) study terminated due to safety concerns;c)subject can obtain medication from a government sponsored or private health program; or d) therapeutic alternatives become available in local market
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-03-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-03-20
    P. End of Trial
    P.End of Trial StatusOngoing
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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